tbuckley/cabot-search huggingface dataset:
Efficient PD-L1 imaging of murine glioblastoma with FUS-aided immunoPET by leveraging FcRn-antibody interaction
Authors: Céline Chevaleyre, Anthony Novell, Nicolas Tournier, Ambre Dauba, Steven Dubois, Dimitri Kereselidze, Erwan Selingue, Benoit Jego, Bernard Maillère, Benoit Larrat, Hervé Nozach, Charles Truillet
Journal: Theranostics (2023)

Rationale:The passage of antibodies through the blood-brain barrier (BBB) and the blood-tumoral barrier (BTB) is determinant not only to increase the immune checkpoint inhibitors efficacy but also to monitor prognostic and predictive biomarkers such as the programmed death ligand 1 (PD-L1) via immunoPET.Although the involvement of neonatal Fc receptor (FcRn) in antibody distribution has been demonstrated, its function at the BBB remains controversial, while it is unknown at the BTB.In this context, we assessed FcRn's role by pharmacokinetic immunoPET imaging combined with focused ultrasounds (FUS) using unmodified and FcRn low-affinity IgGs targeting PD-L1 in a preclinical orthotopic glioblastoma model.Methods: Transcranial FUS were applied over the whole brain in mice shortly before injecting the anti-PD-L1 IgG 89 Zr-DFO-C4 or its FcRn low-affinity mutant 89 Zr-DFO-C4 Fc-MUT in a syngeneic glioblastoma murine model (GL261-GFP).Brain uptake was measured from PET scans acquired up to 7 days post-injection.Kinetic modeling was performed to compare the brain kinetics of both C4 formats.Results: FUS efficiently enhanced the delivery of both C4 radioligands in the brain with high reproducibility. 89Zr-DFO-C4 Fc-MUT mean concentrations in the brain reached a significant uptake of 3.75±0.41%ID/ccwith FUS against 1.92±0.45%ID/ccwithout, at 1h post-injection.A substantial and similar entry of both C4 radioligands was observed at a rate of 0.163±0.071mL/h/g of tissue during 10.4±4.6min.The impaired interaction with FcRn of 89 Zr-DFO-C4 Fc-MUT significantly decreased the efflux constant from the healthy brain tissue to plasma compared with non-mutated IgG.Abolishing FcRn interaction allows determining the target engagement related to the specific binding as soon as 12h post-injection.Conclusion: Abolishing Fc-FcRn interaction confers improved kinetic properties to 89 Zr-DFO-C4 Fc-MUT for immunoPET imaging.FUS-aided BBB/BTB disruption enables quantitative imaging of PD-L1 expression by glioblastoma tumors within the brain.
Path towards mRNA delivery for cancer immunotherapy from bench to bedside
Authors: Wenfei Chen, Yining Zhu, Jinhan He, Xun Sun
Journal: Theranostics (2023)

Messenger RNA (mRNA) has emerged as a promising therapeutic agent for the prevention and treatment of various diseases. mRNA vaccines, in particular, offer an alternative approach to conventional vaccines, boasting high potency, rapid development capabilities, cost-effectiveness, and safe administration. However, the clinical application of mRNA vaccines is hindered by the challenges of mRNA instability and inefficient
Cost-effectiveness of community-based household tuberculosis contact management for children in Cameroon and Uganda: a modelling analysis of a cluster-randomised trial
Authors: Nyashadzaishe Mafirakureva, Boris K Tchounga, Sushant Mukherjee, Boris Tchakounte Youngui, Bob Ssekyanzi, Leonie Simo, Richard F Okello, Stavia Turyahabwe, Albert Kuate Kuate, Jennifer Cohn, Anca Vasiliu, Martina Casenghi, Daniel Atwine, Maryline Bonnet, Peter J Dodd
Journal: The Lancet Global Health (2023)

WHO recommends household contact management (HCM) including contact screening and tuberculosis-preventive treatment (TPT) for eligible children. The CONTACT trial found increased TPT initiation and completion rates when community health workers were used for HCM in Cameroon and Uganda.
The PNPLA3 I148M variant increases ketogenesis and decreases hepatic de novo lipogenesis and mitochondrial function in humans
Authors: Panu K. Luukkonen, Kimmo Porthan, Noora Ahlholm, Fredrik Rosqvist, Sylvie Dufour, Xian-Man Zhang, Tiina E. Lehtimäki, Wenla Seppänen, Marju Orho-Melander, Leanne Hodson, Kitt Falk Petersen, Gerald I. Shulman, Hannele Yki-Järvinen
Journal: Cell Metabolism (2023)

The PNPLA3 I148M variant is the major genetic risk factor for all stages of fatty liver disease, but the underlying pathophysiology remains unclear. We studied the effect of this variant on hepatic metabolism in homozygous carriers and non-carriers under multiple physiological conditions with state-of-the-art stable isotope techniques. After an overnight fast, carriers had higher plasma β-hydroxybutyrate concentrations and lower hepatic de novo lipogenesis (DNL) compared to non-carriers. After a mixed meal, fatty acids were channeled toward ketogenesis in carriers, which was associated with an increase in hepatic mitochondrial redox state. During a ketogenic diet, carriers manifested increased rates of intrahepatic lipolysis, increased plasma β-hydroxybutyrate concentrations, and decreased rates of hepatic mitochondrial citrate synthase flux. These studies demonstrate that homozygous PNPLA3 I148M carriers have hepatic mitochondrial dysfunction leading to reduced DNL and channeling of carbons to ketogenesis. These findings have implications for understanding why the PNPLA3 variant predisposes to progressive liver disease.
MK8722 initiates early-stage autophagy while inhibiting late-stage autophagy via FASN-dependent reprogramming of lipid metabolism
Authors: Luhui Wang, Haiyan Zhu, Zhehao Shi, Bo Chen, Huirong Huang, Ganglian Lin, Jiacheng Li, Haitao Yu, Shihao Xu, Gang Chen, Rongying Ou, Chunxiu Dai
Journal: Theranostics (2023)

Epithelial ovarian cancer (EOC) is associated with latent onset and poor prognosis, with drug resistance being a main concern in improving the prognosis of these patients. The resistance of cancer cells to most chemotherapeutic agents can be related to autophagy mechanisms. This study aimed to assess the therapeutic effect of MK8722, a small-molecule compound that activates AMP-activated protein kinase (AMPK), on EOC cells and to propose a novel strategy for the treatment of EOC.
Efficacy of Sotagliflozin in Adults With Type 2 Diabetes in Relation to Baseline Hemoglobin A1c
Authors: Rahul Aggarwal, Deepak L. Bhatt, Michael Szarek, Christopher P. Cannon, Darren K. McGuire, Silvio E. Inzucchi, Renato D. Lopes, Michael J. Davies, Phillip Banks, Bertram Pitt, Philippe Gabriel Steg
Journal: Journal of the American College of Cardiology (2023)

The SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) and SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trials demonstrated that sotagliflozin, an SGLT1 and SGLT2 inhibitor, improves outcomes in individuals with type 2 diabetes who have heart failure (HF) or kidney disease.We assessed the efficacy of sotagliflozin on HF clinical outcomes in individuals with differing baseline glycosylated hemoglobin (HbA1c) levels.We included all adults from SCORED and SOLOIST-WHF. The primary outcome was a composite of cardiovascular death, hospitalizations for HF, and urgent visits for HF. The efficacy of sotagliflozin compared with placebo was evaluated by baseline HbA1c using competing-risk marginal proportional hazards models.We identified 11,744 adults. Individuals with HbA1c ≤7.5% experienced the primary outcome at a lower rate in the sotagliflozin group (11.2 per 100 person-years) than the placebo group (15.5 per 100 person-years) (HR: 0.73; 95% CI: 0.57-0.93). Similarly, individuals with HbA1c of 7.6% to 9.0% experienced the primary outcome at a lower rate in the sotagliflozin group (7.3 per 100 person-years) than the placebo group (9.4 per 100 person-years) (HR: 0.77; 95% CI: 0.63-0.96). These findings were also consistent among individuals with HbA1c >9.0%, with a primary outcome rate in the sotagliflozin group (7.8 per 100 person-years) that was lower than the placebo group (11.6 per 100 person-years) (HR: 0.65; 95% CI: 0.50-0.84). The efficacy of sotagliflozin was consistent by baseline HbA1c level (P for interaction = 0.58).In individuals with type 2 diabetes and either HF or kidney disease, sotagliflozin reduced HF outcomes irrespective of baseline HbA1c.
Sphingosine 1-Phosphate Receptor Modulators are Effective in Patients With Moderately to Severely Active Ulcerative Colitis and a Prior Biologic Exposure: A Meta-Analysis of Randomized Controlled Trials
Authors: Omar Mahmud, Asad Saulat Fatimi, Muhammad Umar Mahar, Arshia Jahangir, Manzar Abbas, Jeffrey A Berinstein
Journal: Clinical Gastroenterology and Hepatology (2023)
Stress Perfusion Cardiac Magnetic Resonance vs SPECT Imaging for Detection of Coronary Artery Disease
Authors: Andrew E. Arai, Jeanette Schulz-Menger, Dipan J. Shah, Yuchi Han, W. Patricia Bandettini, Arun Abraham, Pamela K. Woodard, Joseph B. Selvanayagam, Christian Hamilton-Craig, Ru-San Tan, James Carr, Lynette Teo, Christopher M. Kramer, Bernd J. Wintersperger, Mukesh G. Harisinghani, Scott D. Flamm, Matthias G. Friedrich, Igor Klem, Subha V. Raman, Daniel Haverstock, Zheyu Liu, Guenther Brueggenwerth, Marta Santiuste, Daniel S. Berman, Dudley J. Pennell
Journal: Journal of the American College of Cardiology (2023)
10-day decitabine versus 3 + 7 chemotherapy followed by allografting in older patients with acute myeloid leukaemia: an open-label, randomised, controlled, phase 3 trial
Authors: Michael Lübbert, Pierre W Wijermans, Michal Kicinski, Sylvain Chantepie, Walter J F M Van der Velden, Richard Noppeney, Laimonas Griškevičius, Andreas Neubauer, Martina Crysandt, Radovan Vrhovac, Mario Luppi, Stephan Fuhrmann, Ernesta Audisio, Anna Candoni, Olivier Legrand, Robin Foà, Gianluca Gaidano, Danielle van Lammeren-Venema, Eduardus F M Posthuma, Mels Hoogendoorn, Anne Giraut, Marian Stevens-Kroef, Joop H Jansen, Aniek O de Graaf, Fabio Efficace, Emanuele Ammatuna, Jean-Pierre Vilque, Ralph Wäsch, Heiko Becker, Nicole Blijlevens, Ulrich Dührsen, Frédéric Baron, Stefan Suciu, Sergio Amadori, Adriano Venditti, Gerwin Huls
Journal: The Lancet Haematology (2023)
Effectiveness of a community-based approach for the investigation and management of children with household tuberculosis contact in Cameroon and Uganda: a cluster-randomised trial
Authors: Maryline Bonnet, Anca Vasiliu, Boris K Tchounga, Benjamin Cuer, Katherine Fielding, Bob Ssekyanzi, Boris Tchakounte Youngui, Jennifer Cohn, Peter J Dodd, Georges Tiendrebeogo, Patrice Tchendjou, Leonie Simo, Richard F Okello, Albert Kuate Kuate, Stavia Turyahabwe, Daniel Atwine, Stephen M Graham, Martina Casenghi
Journal: The Lancet Global Health (2023)

Globally, the uptake of tuberculosis-preventive treatment (TPT) among children with household tuberculosis contact remains low, partly due to the necessity of bringing children to health facilities for investigations. This study aimed to evaluate the effect on TPT initiation and completion of community-based approaches to tuberculosis contact investigations in Cameroon and Uganda.
Abstract 12041: Therapeutic Effects of Induced Pluripotent Stem Cells Secretome In Monocrotaline-induced Pulmonary Arterial Hypertension Rats
Authors: Wei-Chun Huang, Meng-Wei Ke, Chin-Chang Cheng, Shih-Hwa Chiou, Shue-Ren Wann, Chih-Wen Shu, Kuan-Rau Chiou, Ching-Jiunn Tseng, Min-Ci Shen, Wan-Tin Huang, Tzu Jung Li, Pei-leun Kang, Guang-Yuan Mar, Chun-Peng Liu
Journal: Circulation (2015)

Introduction: Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by the increased vascular resistance and the remodeling of pulmonary arteries. Evidences of accumulated inflammatory cells in the lung suggested that chronic inflammation might play a role in PAH. Regenerative cell therapy emerged as a potential treatment for PAH through regulating the host’s immune response. Hypothesis: The secretome of induced pluripotent stem cells (iPSCs) was investigated for their preventive and therapeutic effects in the pathogenesis of monocrotaline (MCT)-induced PAH rat. Methods: PAH was developed by the subcutaneous injection of MCT in rats. The conditioned medium of cultured iPSCs (iPSC CM) was applied daily in prevention (an hour after MCT injection) or reversal (14 days after MCT injection) by IP injection throughout the full 28 days of experiment. The effects of iPSC CM were interpreted by the analyses of systolic pressure (RVSP) and the hypertrophy index of right ventricle, also the regulation of inflammation in lung and the underlying mechanism. Results: Both prevention and reversal, the hemodynamic values of RVSP and hypertrophy index were significantly improved in MCT-induced PAH rats after iPSC CM treatment. Attenuated expression of pro-inflammatory M1 macrophage markers was observed in either the lung of MCT-induced PAH rats or in co-cultured human M1 macrophages after iPSC CM treatment. To investigate the potential molecules secreted by iPSCs into iPSC CM, two major ingredients, named α1-antitrypsin and feutin-a, were identified by protein mass spectrometry and confirmed by western blotting with specific antibodies. Both components were mentioned to be involved in the anti-inflammatory effects observed in various lung diseases. Conclusions: In this study, iPSC CM represented therapeutic benefits on MCT-induced PAH rats though attenuating inflammation. Molecules exhibit anti-inflammatory potential existed in the iPSC CM, such as α1-antitrypsin and feutin-a, might hold the promise as new therapeutics of regenerative cell therapy via paracrine mechanism.
Economic Costs of Diabetes in the U.S. in 2022
Authors: Emily D. Parker, Janice Lin, Troy Mahoney, Nwanneamaka Ume, Grace Yang, Robert A. Gabbay, Nuha A. ElSayed, Raveendhara R. Bannuru
Journal: Diabetes Care (2023)

This study updates previous estimates of the economic burden of diagnosed diabetes, with calculation of the health resource use and indirect costs attributable to diabetes in 2022.We combine the demographics of the U.S. population in 2022 with diabetes prevalence, from national survey data, epidemiological data, health care cost data, and economic data, into a Cost of Diabetes Economic Model to estimate the economic burden at the population and per capita levels. Health resource use and associated medical costs are analyzed by age, sex, race/ethnicity, comorbid condition, and health service category. Data sources include national surveys (2015-2020 or most recent available), Medicare standard analytic files (2020), and administrative claims data from 2018 to 2021 for a large commercially insured population in the U.S.The total estimated cost of diagnosed diabetes in the U.S. in 2022 is $412.9 billion, including $306.6 billion in direct medical costs and $106.3 billion in indirect costs attributable to diabetes. For cost categories analyzed, care for people diagnosed with diabetes accounts for 1 in 4 health care dollars in the U.S., 61% of which are attributable to diabetes. On average people with diabetes incur annual medical expenditures of $19,736, of which approximately $12,022 is attributable to diabetes. People diagnosed with diabetes, on average, have medical expenditures 2.6 times higher than what would be expected without diabetes. Glucose-lowering medications and diabetes supplies account for ∼17% of the total direct medical costs attributable to diabetes. Major contributors to indirect costs are reduced employment due to disability ($28.3 billion), presenteeism ($35.8 billion), and lost productivity due to 338,526 premature deaths ($32.4 billion).The inflation-adjusted direct medical costs of diabetes are estimated to rise 7% from 2017 and 35% from 2012 calculations (stated in 2022 dollars). Following decades of steadily increasing prevalence of diabetes, the overall estimated prevalence in 2022 remains relatively stable in comparison to 2017. However, the absolute number of people with diabetes has grown and contributes to increased health care expenditures, particularly per capita spending on inpatient hospital stays and prescription medications. The enormous economic toll of diabetes continues to burden society through direct medical and indirect costs.
Thermodynamically stable ionic liquid microemulsions pioneer pathways for topical delivery and peptide application
Authors: Tianqi Liu, Ying Liu, Xiaoyu Zhao, Liguo Zhang, Wei Wang, De Bai, Ya Liao, Zhenyuan Wang, Mi Wang, Jiaheng Zhang
Journal: Bioactive Materials (2023)

Copper peptides (GHK-Cu) are a powerful hair growth promoter with minimal side effects when compared with minoxidil and finasteride; however, challenges in delivering GHK-Cu topically limits their non-invasive applications. Using theoretical calculations and pseudo-ternary phase diagrams, we designed and constructed a thermodynamically stable ionic liquid (IL)-based microemulsion (IL-M), which integrates the high drug solubility of ILs and high skin permeability of microemulsions, thus improving the local delivery of copper peptides by approximately three-fold while retaining their biological function. Experiments in mice validated the effectiveness of our proposed IL-M system. Furthermore, the exact effects of the IL-M system on the expression of growth factors, such as vascular endothelial growth factor, were revealed, and it was found that microemulsion increased the activation of the Wnt/β-catenin signaling pathway, which includes factors involved in hair growth regulation. Overall, the safe and non-invasive IL microemulsion system developed in this study has great potential for the clinical treatment of hair loss.
Inhibiting the Inhibitor in Synovial Macrophages and Cancer Immunotherapy–Associated Inflammatory Arthritis
Authors: Nisarg J. Shah, Nunzio Bottini
Journal: Arthritis & Rheumatology (2023)

Disclosure form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Dipicolylamine‐Zn Induced Targeting and Photo‐Eliminating of <i>Pseudomonas aeruginosa</i> and Drug‐Resistance Gram‐Positive Bacteria
Authors: Zuokai Wang, Wenlin Cai, Fangrui Ning, Wen Sun, Jianjun Du, Saran Long, Jiangli Fan, Xiaoqiang Chen, Xiaojun Peng
Journal: Advanced Healthcare Materials (2023)

The emergence of drug-resistant bacteria, particularly resistant strains of Gram-negative bacteria, such as Pseudomonas aeruginosa, poses a significant threat to public health. Although antibacterial photodynamic therapy (APDT) is a promising strategy for combating drug-resistant bacteria, actively targeted photosensitizers (PSs) remain unknown. In this study, a PS based on dipicolylamine (DPA), known as WZK-DPA-Zn, is designed for the selective identification of P. aeruginosa and drug-resistant Gram-positive bacteria. WZK-DPA-Zn exploits the synergistic effects of DPA-Zn
The effect of a Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP) coating on the chronic recording performance of planar silicon intracortical microelectrode arrays
Authors: Ana G. Hernandez-Reynoso, Brandon S. Sturgill, George F. Hoeferlin, Lindsey N. Druschel, Olivia K. Krebs, Dhariyat M. Menendez, Teresa T.D. Thai, Thomas J. Smith, Jonathan Duncan, Jichu Zhang, Gaurav Mittal, Rahul Radhakrishna, Mrudang Spandan Desai, Stuart F. Cogan, Joseph J. Pancrazio, Jeffrey R. Capadona
Journal: Biomaterials (2023)

Intracortical microelectrode arrays (MEAs) are used to record neural activity. However, their implantation initiates a neuroinflammatory cascade, involving the accumulation of reactive oxygen species, leading to interface failure. Here, we coated commercially-available MEAs with Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP), to mitigate oxidative stress. First, we assessed the in vitro cytotoxicity of modified sample substrates. Then, we implanted 36 rats with uncoated, MnTBAP-coated ("Coated"), or (3-Aminopropyl)triethoxysilane (APTES)-coated devices - an intermediate step in the coating process. We assessed electrode performance during the acute (1-5 weeks), sub-chronic (6-11 weeks), and chronic (12-16 weeks) phases after implantation. Three subsets of animals were euthanized at different time points to assess the acute, sub-chronic and chronic immunohistological responses. Results showed that MnTBAP coatings were not cytotoxic in vitro, and their implantation in vivo improved the proportion of electrodes during the sub-chronic and chronic phases; APTES coatings resulted in failure of the neural interface during the chronic phase. In addition, MnTBAP coatings improved the quality of the signal throughout the study and reduced the neuroinflammatory response around the implant as early as two weeks, an effect that remained consistent for months post-implantation. Together, these results suggest that MnTBAP coatings are a potentially useful modification to improve MEA reliability.
Nirmatrelvir/ritonavir use in pregnant women with SARS-CoV-2 Omicron infection: a target trial emulation
Authors: Carlos K. H. Wong, Kristy T. K. Lau, Matthew S. H. Chung, Ivan C. H. Au, Ka Wang Cheung, Eric H. Y. Lau, Yasmin Daoud, Benjamin J. Cowling, Gabriel M. Leung
Journal: Nature Medicine (2023)
Correction Notice: Inferior Outcomes of EU Versus US Patients Treated With CD19 CAR-T for Relapsed/Refractory Large B-cell Lymphoma: Association With Differences in Tumor Burden, Systemic Inflammation, Bridging Therapy Utilization, and CAR-T Product Use
Journal: HemaSphere (2023)

[This corrects the article DOI: 10.1097/HS9.0000000000000907.].
The effect of combination prevention strategies on HIV incidence among gay and bisexual men who have sex with men in the UK: a model-based analysis
Authors: Valentina Cambiano, Alec Miners, Fiona C Lampe, Sheena McCormack, O Noel Gill, Graham Hart, Kevin A Fenton, Gus Cairns, Marc Thompson, Valerie Delpech, Alison J Rodger, Andrew N Phillips
Journal: The Lancet HIV (2023)

In the UK, the number of new HIV diagnoses among gay and bisexual men who have sex with men (GBMSM) has decreased substantially. We aimed to understand the contribution of different interventions in reducing HIV incidence so far; to estimate future HIV incidence with continuation of current policies and with further scaling up of current interventions; and to estimate the maximum additional annual cost that should be spent towards these interventions for them to offer value for money.
Integrase strand-transfer inhibitor use and cardiovascular events in adults with HIV: an emulation of target trials in the HIV-CAUSAL Collaboration and the Antiretroviral Therapy Cohort Collaboration
Authors: Sophia M Rein, Sara Lodi, Roger W Logan, Giota Touloumi, Anastasia Antoniadou, Linda Wittkop, Fabrice Bonnet, Ard van Sighem, Marc van der Valk, Peter Reiss, Marina B Klein, James Young, Inmaculada Jarrin, Antonella d'Arminio Monforte, Alessandro Tavelli, Laurence Meyer, Laurent Tran, Michael J Gill, Raynell Lang, Bernard Surial, Andreas D Haas, Amy C Justice, Christopher T Rentsch, Andrew Phillips, Caroline A Sabin, Jose M Miro, Adam Trickey, Suzanne M Ingle, Jonathan A C Sterne, Miguel A Hernán
Journal: The Lancet HIV (2023)
Management of Bleeding Due to Small-Intestinal Angiodysplasias
Authors: Loren Laine
Journal: New England Journal of Medicine (2023)

The small intestine is estimated to be the source of bleeding in approximately 5 to 10% of patients with gastrointestinal bleeding, and angiodysplasias are the most common cause of small-intestinal bleeding.1,2 Advances in endoscopy (e.g., video capsule endoscopy and deep enteroscopy) have increased the ability to diagnose small-intestinal angiodysplasias that cause bleeding and to treat affected patients, but they have not clearly led to improved long-term outcomes.2,3 Endoscopic therapy is commonly used to treat small-intestinal angiodysplasias, although supporting evidence is generally of very low quality, and most studies fail to document long-term efficacy. Pooled incidences of rebleeding after endoscopic therapy . . .